Abstract 19809: Heparin Binding EGF-Like Growth Factor (HB-EGF) is a Novel Regulator for Hyperlipidemia

Objective: Elevation of ApoB-containing lipoproteins in circulation a well-established risk factor for the development of cardiovascular diseases. HB-EGF, which is an endogenous ligand of EGFR and ERBB4, was reported to be positively associated with blood lipid level in human individuals. In this study, we tested the effects of HB-EGF targeting on the induction of hyperlipidemia and hyperlipidemia-induced vascular diseases atherosclerosis and aneurysm in a mouse model. Methods and Results: LDLR deficient mice were fed a high fat diet (HFD, 21% fat and 0.2% cholesterol) throughout the study for the induction of hyperlipidemia and atherosclerosis. For aneurysm study, we added 28-day of angiotensin II infusion (1,000ng/kg/min) via osmotic mini-pump installation as a final step. For HB-EGF targeting, the mice were injected intraperitoneally with control or HB-EGF antisense oligonucleotide (ASO) for 12 weeks. At termination step, we measured lipid concentrations in circulation, aortic lesion size, and thoracic...